FDA Submission Filed for Neladalkib in ALK+ Lung Cancer

Nuvalent, Inc. announced that it has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for neladalkib, an investigational treatment for patients with advanced ALK-positive non-small cell lung cancer who have previously received tyrosine kinase inhibitors, aiming to expand treatment options for this patient population.

Main data that support the findings

The application is based on findings from the global ALKOVE-1 phase 1/2 clinical trial, which evaluated neladalkib in patients with advanced ALK-positive non-small cell lung cancer who had already been treated with tyrosine kinase inhibitors. In this group, the therapy showed encouraging overall activity.

According to the company, responses were observed not only in tumors throughout the body but also in the brain, highlighting intracranial activity. This is particularly relevant for patients with cancer that has spread to the central nervous system. Neladalkib was also reported to address key drivers of disease progression, including resistance mechanisms that can develop after earlier lines of targeted therapy.

The safety profile was described as generally well tolerated and consistent with its design as an ALK-selective, TRK-sparing inhibitor. This design aims to limit certain central nervous system side effects associated with therapies that also target TRK.

Neladalkib has received breakthrough therapy designation from the FDA for patients with locally advanced or metastatic ALK-positive non-small cell lung cancer who have previously been treated with two or more ALK tyrosine kinase inhibitors. It has also been granted orphan drug designation for this disease.

Trial details of ALKOVE-1

The ALKOVE-1 trial is a first-in-human phase 1/2 clinical study evaluating neladalkib in patients with advanced ALK-positive non-small cell lung cancer and other solid tumors.

In the completed phase 1 portion, patients with ALK-positive non-small cell lung cancer who had received at least one prior ALK tyrosine kinase inhibitor were enrolled, along with patients who had other ALK-positive solid tumors and had either received prior treatment or had no satisfactory standard treatment options. This portion of the study focused on assessing safety and tolerability, determining the recommended phase 2 dose, evaluating how the drug moves through the body and identifying early signs of anti-tumor activity.

The phase 2 portion of the trial is ongoing and is designed as a global, single-arm, open-label study with registrational intent. It focuses on patients with advanced ALK-positive non-small cell lung cancer who have previously been treated with tyrosine kinase inhibitors.

Enrollment is still ongoing in certain groups, including adult and adolescent patients with ALK-positive solid tumors outside of non-small cell lung cancer, as well as adolescent patients with ALK-positive non-small cell lung cancer.

Neladalkib is designed to penetrate the brain and remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors. This includes tumors with specific resistance mutations such as G1202R. The therapy is also designed to avoid targeting the TRK family of proteins, which may help reduce certain central nervous system side effects.

Safety of neladalkib

In the ALKOVE-1 trial, neladalkib demonstrated a generally well-tolerated safety profile in patients with cancer who had previously received tyrosine kinase inhibitors. The safety findings were described as consistent with the drug’s ALK-selective and TRK-sparing design.

By avoiding inhibition of TRK proteins, neladalkib may help reduce central nervous system side effects that have been observed with treatments that target both ALK and TRK. The company noted that this design could support improved tolerability while maintaining anti-tumor activity.

Detailed safety and efficacy results from the trial have not yet been fully reported, and the company plans to present additional data at a future medical meeting.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

1. “Nuvalent Announces Submission of New Drug Application to FDA for Neladalkib in TKI Pre-treated Advanced ALK-positive NSCLC” News Release. Nuvalent, Inc., April 7, 2026

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